Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza.

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

Addiction to Tobacco Smoking and Vaping.

The tobacco epidemic has been one of the biggest public health threats, and smoking is one of the world's largest preventable causes of premature death. An estimated 15.4% of all deaths in the world are attributable to tobacco smoking. The present review aims to describe addiction to tobacco smoking and vaping. Tobacco and vaping devices contain nicotine, a highly addictive drug, which explains why smoking is so prevalent and persistent. Electronic cigarettes are a group of novel nicotine or tobacco products that have rapidly gained popularity in recent years. Electronic cigarette devices allow for the use of other drugs, including THC, while the lax regulation may allow for the introduction of toxic compounds that can lead to acute or subacute toxicity, such as the e-cigarette- or vaping-associated lung injury that has been linked to vitamin E acetate. In addition, regular vapers and heated tobacco devices emit toxins, although at lower concentrations than burned tobacco. However, more and more side effects have been identified. No new effective treatment for nicotine addiction has been developed recently, despite its huge adverse impact on overall health and other outcomes. As for the primary line of medications, the last one started in 2006, the varenicline, demonstrating a low interest in developing new medications against smoking, an unacceptable state of affairs, given the huge impact of smoking on morbidity and mortality.

Associated risks of smoking and possible benefits of cessation in Covid-19: a rapid narrative review.

OBJECTIVE: To describe the possible risks associated to smoking in the spread and complications of Covid-19, em-phasizing in the benefits of quitting smoking. MATERIALS AND METHODS: The narrative review methodology and the established process for Cochrane rapid reviews were used. RESULTS: The scientific evidence related to smoking and Covid-19 remains limited. However, there is an already documented trend in cross-sectional, clinical studies and meta-analyses on the increased risk of adverse outcomes with Covid-19 associated with tobacco use. CONCLUSIONS: It is necessary to issue a warning that persons who smoke would have greater risks in the Covid-19 pandemic, which add to the many already known risks of tobacco use. Thus, quitting smoking becomes a relevant preventive measure to better confront SARS-CoV-2.

Feeding intolerance during prolonged prone position in overweight and obese patients with severe COVID-19.

Introduction: Objective: the aim of this study was to compare the incidence rate of feeding intolerance (FI) during supine (SP) or prone positioning (PP) in critically ill COVID-19 patients. Methods: this was a retrospective cohort study of critically ill patients with overweight or obesity who received enteral nutrition (EN) in prone or supine positioning continuously during the first five days of mechanical ventilation. Nutritional risk, anthropometric measurements and body composition were assessed at the first 24 hours upon Intensive Care Unit (ICU) admission. Biochemical and clinical variables (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Kidney Injury [AKI] or comorbidities diagnosis) were collected. Pharmacotherapy (prokinetics, sedatives or neuromuscular blocking agents) and FI incidence (gastric residual volume [GRV] ≥ 200 ml or ≥ 500 ml, vomiting or diarrhea) were daily recorded. Constipation was defined as the absence of evacuation for five consecutive days. Results: eighty-two patients were included. Higher rate of prophylactic prokinetic prescription was observed in PP (42.8 vs 12.5 %, p = 0.002). GRV ≥ 200 in supine position was not different when compared to PP (p = 0.47). Vomiting episodes in supine compared to PP showed no difference between groups (15 % vs 24 %, p = 0.31). No differences in diarrhea events were detected (10 % vs 4.7 %, p = 0.36). Constipation was common in both groups (95 % vs 82 %, p = 0.06). Conclusion: FI during prone position was not different in comparison to supine position. Routinely use of prokinetics in continuous prone position may help to prevent FI incidence. Algorithm development is necessary for FI prevention and treatment so to avoid EN interruptions and adverse clinical outcomes.

Introducción: Objetivo: comparar la incidencia de intolerancia a la alimentación entre pacientes críticos en posición supino (PS) o prono (PP). Métodos: cohorte retrospectiva de pacientes bajo ventilación mecánica por distrés respiratorio por COVID-19 y sobrepeso y obesidad, quienes recibieron nutrición enteral (NE) en PP o PS. Se evaluaron riesgo nutricional, mediciones antropométricas y composición corporal en las primeras 24 horas de ingreso a la Unidad de Cuidados Intensivos (UCI). Se recolectaron variables bioquímicas y clínicas (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation II [APACHE II], lesión renal aguda y otras comorbilidades). Se registró el esquema de farmacoterapia prescrita durante los primeros cinco días (procinéticos, sedantes y bloqueadores neuromusculares). Se evaluó la incidencia de intolerancia a la alimentación, definida como la presencia de residuo gástrico (RG) ≥ 200 o ≥ 500 ml, vómito, diarrea o estreñimiento. Resultados: fueron incluidos 82 pacientes. Se observó una mayor prescripción de procinéticos como terapia profiláctica en PP (42,8 vs. 12,5 %, p = 0,002). No se observaron diferencias en RG ≥ 200 ml (p = 0,47) ni vómito (p = 0,31) entre ambos grupos. No se observaron diferencias en episodios de diarrea (10 % en PS vs. 4,7 % en PP, p = 0,36). El estreñimiento fue común en ambos grupos de estudio (95 vs. 82 %, p = 0,06). Conclusiones: la PP no se relaciona con una mayor incidencia de intolerancias a la alimentación. El uso rutinario de procinéticos durante la PP continua puede ayudar a prevenir la incidencia de dichas intolerancias. Es necesario el desarrollo de algoritmos para la prevención y tratamiento de las intolerancias a la alimentación para evitar interrupciones en la NE y desenlaces no deseables.

Low phase angle is associated with 60-day mortality in critically ill patients with COVID-19.

BACKGROUND: Malnutrition status, body composition indicators, and bioelectrical impedance analysis (BIA) parameters have been associated with increased risk of death in several pathologies. The aim of this study was to describe the associations between phase angle (PhA) indicators obtained by BIA with length of hospital stay, days on mechanical ventilation, and 60-day mortality in critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a prospective cohort of mechanically ventilated patients with coronavirus disease 2019 (COVID-19). We assessed nutrition risk and body composition with BIA within 48 h from intensive care unit admission. Logistic and linear regression models were used to analyze the association between variables and clinical outcomes. Survival analysis by PhA value was performed using Kaplan-Meier curves. RESULTS: Sixty-seven patients were included. PhA (odds ratio [OR], 0.36; P = .002), standardized PhA (SPA) (OR, 0.45; P = .001), and extracellular water/total body water ratio (OR, 3.25; P = .002) were significant predictors of 60-day mortality. PhA <3.85° in females and <5.25° in males showed good and fair discrimination, respectively, for mortality prediction. Using cutoff values, low PhA was associated with a significantly increased risk of 60-day mortality (hazard ratio, 3.08; 95% CI, 1.12-8.41; P = .02). No association was detected for SPA. CONCLUSION: Low PhA values could be a predictor of 60-day mortality in critically ill patients with COVID-19. This biological marker could be incorporated as part of nutrition and mortality risk assessment in this population.

High nutritional risk using NUTRIC-Score is associated with worse outcomes in COVID-19 critically ill patients.

INTRODUCTION: Background: nutritional risk has been associated with worse outcomes at the critical care unit. The aim of this study was to describe the association between nutritional risk and length of stay, days on mechanical ventilation, and in-hospital mortality in patients infected with SARS-CoV-2. Methods: a retrospective cohort of ventilated, critically ill patients. We assessed nutrition risk at baseline using NUTRIC-score. Logistic and linear regression models were used to analyze the association between NUTRIC-score and clinical outcomes (days on mechanical ventilation, hospital length of stay, and in-hospital mortality). A survival analysis was performed using Kaplan-Meier curves. Results: a total of 112 patients were included, 39.3 % were overweight and 47.3 % were obese. Based on NUTRIC-Score, 66 % and 34 % of patients were at high and low nutritional risk, respectively. High nutritional risk was associated with increased mortality risk (OR: 2.4, 95 % CI, 1.06-5.47, p = 0.036) and higher 28-day mortality (HR: 2.05, 95 % CI, 1.01-4.23, p = 0.04) in comparison with low risk. Conclusion: high nutritional risk is related to mortality in SARS-CoV-2 critically ill patients. Overweight and obesity are common in this sample. More studies are needed to elucidate the impact of nutritional therapy on infection course and outcomes.

INTRODUCCIÓN: Introducción: el riesgo nutricional se asocia a peores desenlaces en los pacientes en estado crítico. El objetivo de este estudio es describir la asociación entre el riesgo nutricional y los días de estancia hospitalaria, los días de ventilación mecánica y la mortalidad en pacientes infectados por el SARS-CoV-2. Métodos: cohorte retrospectiva de pacientes en estado crítico bajo ventilación mecánica invasiva. Se evaluó el riesgo nutricional utilizando la herramienta NUTRIC-Score. Se utilizaron regresiones lineares y logísticas para evaluar la asociación entre el riesgo nutricional y los desenlaces clínicos (días de ventilación mecánica, días de estancia hospitalaria y mortalidad hospitalaria). Se utilizaron curvas de Kaplan-Meier para analizar la sobrevivencia. Resultados: se incluyeron 112 pacientes, el 39,3 % con diagnóstico de sobrepeso y el 47,3 % con obesidad de acuerdo con el IMC. Utilizando la herramienta NUTRIC-Score, el 66 % tenían riesgo nutricional alto y el 34 % riesgo nutricional bajo. El riesgo nutricional alto se asoció a un mayor riesgo de mortalidad (OR: 2,4; IC 95 %: 1,06-5,47; p = 0,036) y mayor mortalidad a 28 días (HR: 2,05; IC 95 %: 1,01-4,23; p = 0,04) en comparación con los individuos con riesgo nutricional bajo. Conclusión: el riesgo nutricional alto se asocia con mortalidad en los pacientes con infección por SARS-CoV-2 en estado crítico. El sobrepeso y la obesidad son comunes en este grupo de pacientes. Se necesitan más estudios que evalúen el impacto de la terapia nutricional sobre el curso de la infección y los desenlaces clínicos.

Safety and tolerance of enteral nutrition in COVID-19 critically ill patients, a retrospective study.

BACKGROUND: There is a lack of evidence about the tolerance of enteral nutrition (EN) in COVID-19 critically ill patients. However, several gastrointestinal manifestations related to COVID-19 have been described. The aims of this study were to analyze the incidence of gastrointestinal intolerance (GI) associated to EN (diarrhea, vomiting, gastroparesis and constipation) and to describe energy/protein provision along with biochemical alterations during the first week of EN. METHODS: A retrospective cohort of COVID-19 critically ill patients under mechanical ventilation. We reported daily enteral nutrition infusion and gastrointestinal manifestations within the first week of intubation and enteral nutrition initiation. RESULTS: Fifty-two patients were included; 40.3% were overweight and 46.2% were obese. During the first 7 days of EN, manifestations of GI intolerance such as vomiting, diarrhea and gastroparesis were present in 18 patients (32.4%). Hypernatremia (39%) was the most frequent electrolyte abnormality. Only Acute Kidney Injury (AKI) diagnosis was associated with a higher energy deficit on day 7. No associations between drug prescription and GI intolerance were observed. On day 4, 94.5% of patients were receiving more than 80% of energy requirements and 94.2% of protein requirements. Accumulated energy and protein deficits at day 3 were 2171.2 ± 945 kcal and 114.9 ± 49.2 g, respectively; and 2586.4 ± 1151 kcal, 133.3 ± 60.4 g at day 7. CONCLUSION: Enteral nutrition is feasible and well-tolerated in COVID-19 patients with mechanical ventilation within the first week of enteral nutrition initiation. More studies are needed to elucidate the impact of nutritional therapy on infection course and outcomes.

Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: A randomized controlled trial.

INTRODUCTION: The novel coronavirus pandemic (COVID-19) represents a major public health problem and it is key to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo. MATERIAL AND METHODS: A double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events. RESULTS: A total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% ± 20, tachycardic (pulse rate 108±17 min-1) and tachypneic (32 ±10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes. CONCLUSION: No beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19.

Clinical Markers of Chronic Hypoxemia in Respiratory Patients Residing at Moderate Altitude.

Supplemental oxygen (SO) increases survival in hypoxemic patients. In hypoxia, mammals respond by modulating O2-sensitive transducers that stabilize the transcription factor hypoxia-inducible factor-1-alpha (HIF-1α), which transactivates the genes that govern angiogenesis and metabolic pathways. Residing at high altitudes exposes millions of people to hypoxemia with potential adverse consequences on their health. We aimed to identify markers of hypoxemia that can be used in the evaluation of patients in addition to pulse oximetry and arterial blood gases, especially those that could respond after 1 month of oxygen use. We performed a prospective pilot study at 2240 m above sea level, with repeated measurements before and after (b/a) 1-month home oxygen therapy in 70 patients with lung diseases, of which 24/20 have COPD, 41/39 obstructive sleep apnea (OSA), and 5/2 with interstitial lung diseases (ILD), all of them having chronic hypoxemia, as well as 70 healthy subjects as controls. Proteins evaluated included HIF-1α, vascular endothelial growth factor (VEGF), and erythropoietin (EPO). Among the main results, we found that hypoxemic patients had normal levels of HIF-1α but increased EPO compared with healthy controls. VEGF levels were heterogeneous in the sample studied, similar to the control group in COPD, slightly increased in OSA, and decreased in fibrosis. With oxygen treatment, the HIF-1α and EPO decreased in COPD and OSA but not in fibrosis, and VEGF remained constant over time. In conclusion, erythropoietin and HIF-1α identified hypoxemia initially and responded to oxygen. In pulmonary fibrosis, HIF-1α, EPO, and VEGF increased with oxygen therapy, which is likely linked to the disease's pathogenesis and clinical course rather than hypoxemia.

Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes.

The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.

The SNP rs13147758 in the HHIP Gene Is Associated With COPD Susceptibility, Serum, and Sputum Protein Levels in Smokers.

BACKGROUND: Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican mestizo smokers. MATERIALS AND METHODS: Association analysis was performed by carrying out a case-control study in Mexican mestizo smokers comprised of two groups: tobacco-smoking subjects with COPD (COPD-TS, n = 222) and smokers without COPD (SWOC, n = 333). We evaluated three SNPs (rs13147758, rs1828591, and rs13118928) in the HHIP gene. Allele discrimination was accomplished by qPCR using TaqMan probes, and determination of protein levels in the serum and sputum supernatants (SS) was performed using ELISA. RESULTS: Statistically significant differences were observed in the rs13147758 GG genotype (adjusted p = 0.014, OR = 1.95) and the rs13147758-rs1828591 GA haplotype (p = 6.6E-06, OR = 2.65) in the case-control comparison. HHIP protein levels were elevated in SS samples from the COPD-TS group compared to those from the SWOC group (p = 0.03). Based on genotype analysis, HHIP protein levels were lower in the serum samples of rs13147758 GG genotype carriers in the COPD-TS group than in the serum samples of rs13147758 GG genotype carriers from the SWOC group (p < 0.05), but there were no differences in the sputum samples. CONCLUSION: The rs13147758 GG genotype and the rs13147758-rs1828591 GA haplotype are associated with susceptibility to COPD. Furthermore, an association in protein levels was observed between the HHIP rs13147758 genotype and COPD in Mexican mestizo smokers.

Addiction to Tobacco Smoking and Vaping

ABSTRACT The tobacco epidemic has been one of the biggest public health threats, and smoking is one of the world's largest preventable causes of premature death. An estimated 15.4% of all deaths in the world are attributable to tobacco smoking. The present review aims to describe addiction to tobacco smoking and vaping. Tobacco and vaping devices contain nicotine, a highly addictive drug, which explains why smoking is so prevalent and persistent. Electronic cigarettes are a group of novel nicotine or tobacco products that have rapidly gained popularity in recent years. Electronic cigarette devices allow for the use of other drugs, including THC, while the lax regulation may allow for the introduction of toxic compounds that can lead to acute or subacute toxicity, such as the e-cigarette- or vaping-associated lung injury that has been linked to vitamin E acetate. In addition, regular vapers and heated tobacco devices emit toxins, although at lower concentrations than burned tobacco. However, more and more side effects have been identified. No new effective treatment for nicotine addiction has been developed recently, despite its huge adverse impact on overall health and other outcomes. As for the primary line of medications, the last one started in 2006, the varenicline, demonstrating a low interest in developing new medications against smoking, an unacceptable state of affairs, given the huge impact of smoking on morbidity and mortality.

Associated risks of smoking and possible benefits of cessation in Covid-19: a rapid narrative review / Riesgos asociados con tabaquismo y posibles beneficios de cesación en Covid-19: una revisión narrativa rápida

Abstract: Objective: To describe the possible risks associated to smoking in the spread and complications of Covid-19, emphasizing in the benefits of quitting smoking. Materials and methods: The narrative review methodology and the established process for Cochrane rapid reviews were used. Results: The scientific evidence related to smoking and Covid-19 remains limited. However, there is an already documented trend in cross-sectional, clinical studies and meta-analyses on the increased risk of adverse outcomes with Covid-19 associated with tobacco use. Conclusions: It is necessary to issue a warning that persons who smoke would have greater risks in the Covid-19 pandemic, which add to the many already known risks of tobacco use. Thus, quitting smoking becomes a relevant preventive measure to better confront SARS-CoV-2.

Resumen: Objetivo: Describir los posibles riesgos asociados de tabaquismo con contagio y complicaciones por Covid-19, haciendo hincapié en los beneficios de dejar de fumar. Material y métodos: Se utilizó la metodología de revisión narrativa y el proceso establecido para las revisiones rápidas Cochrane. Resultados: La evidencia científica relacionada con el tabaquismo y Covid-19 todavía es limitada. Existe una tendencia ya documentada en estudios clínicos transversales y metaanálisis del aumento del riesgo de resultados adversos para Covid-19 asociados con el consumo de tabaco. Conclusiones: Es necesario advertir que las personas que fuman tendrán mayores riesgos en la pandemia de Covid-19, los cuales se suman a los muchos ya conocidos del consumo de tabaco, de modo que dejar de fumar se convierte en una medida preventiva relevante para enfrentar mejor el SARS-CoV-2.